Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
1. Claims 1-11 are pending and under examination to the extent of the elected species of SEQ ID NO:3, SEQ ID NO:9, and geranylgeranyl diphosphate (GGPP).
Claims 12-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on December 20, 2024.
Information Disclosure Statement
2. The Information Disclosure Statements (IDS) submitted on September 12, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS have been considered. Signed copies are attached.
Response to Arguments – Objections to the Specification
3. Applicant’s arguments and amendments filed August 25, 2025 have overcome the objections of record.
Response to Arguments – Claim Objections
4. Applicant’s arguments and amendments filed August 25, 2025 have overcome the objections of record.
Response to Arguments – Claim Rejections - 35 USC § 112(b)
5. Applicant’s arguments and amendments filed August 25, 2025 have necessitated new rejections under 35 U.S.C. 112(b).
Claim Rejections - 35 USC § 112(b)
6. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
7. Claims 1-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The metes and bounds of claim 1 are indefinite because it is unclear how a protein can comprise 95% sequence identity to two distinct amino acid sequences (SEQ ID NO:1 and SEQ ID NO:3). If Applicant intends to recite a sequence comprising 95% sequence identity to either SEQ ID NO:1 or SEQ ID NO:3, it is recommended Applicant amend the claim accordingly.
Dependent claims are included. Appropriate correction is required.
Response to Arguments – Claim Rejections - 35 USC § 101
8. Applicant’s arguments and amendments filed August 25, 2025 have been fully considered but are not persuasive and do not overcome the rejections of record.
Applicant argues primarily that an agreement was reached in the interview held on August 06, 2025, that amending the claim to recite the preamble “A host cell comprising” and recite SEQ ID NOs:1, 3, and 9 would be sufficient to overcome the rejection of record for lack of utility under 35 USC § 101. However, this is incorrect. As noted in the Examiner’s Interview Summary (dated 08/08/2025), Applicant was advised to amend the claim(s) to recite and require each of SEQ ID NOs:1, 3, and 9, because all three components are required to produce the recited compounds. As amended, claim 1 requires only a single terpene synthase enzyme of either SEQ ID NO:1, SEQ ID NO:3, or some undefined combination of SEQ ID NO:1 and SEQ ID NO:3 (see rejection under 35 USC § 112(b)). Therefore, the claimed host cell may consist of only a single terpene synthase (SEQ ID NO:1 or SEQ ID NO:3) and a single cytochrome P450 enzyme (SEQ ID NO:9), while the specification discloses that both a type I (e.g., SEQ ID NO:1) and type II (e.g., SEQ ID NO:3) terpene synthase are needed in combination with a cytochrome P450 enzyme (e.g., SEQ ID NO:9) to produce the recited diterpenoid alkaloids. Accordingly, the claimed host cell lacks utility and the rejection is maintained.
Claim Rejections - 35 USC § 101
9. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
10. Claims 1-11 are rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility.
Regarding claim 1, the recitation of an expression cassette encoding at least one terpene synthase and at least one cytochrome P450 enzyme encompasses expression cassettes encoding only one terpene synthase and only one cytochrome P450 enzyme.
The specification indicates that the invention provides expression systems that can provide diterpenoid alkaloids and methods for synthesizing diterpenoid alkaloids wherein the methods comprise incubating a host cell comprising said expression systems (p. 01, lns. 20-26; p. 02, lns 1-10). The specification discloses a pathway for the biosynthesis of diterpenoid alkaloids from GGPP comprising two classes of terpene synthases and two cytochrome P450 enzymes (p. 06; “Scheme 1”; p. 54, lns. 6-17). Accordingly, the specification indicates the requirement of a diterpenoid alkaloid precursor such as GGPP for the synthesis of diterpenoid alkaloids in certain host cells (p. 02, lns. 11-12; p. 06; “Scheme 1”).
The specification also discloses SEQ ID NO:3 as the amino acid sequence of Delphinium grandiflorum Type II terpene synthase TPS7a (DgrTPS7a; p. 14, lns. 23-24) and SEQ ID NO:9 as the amino acid sequence of D. grandiflorum cytochrome P450 CYP71FH1 (p. 19, lns. 25-26). Applicant further discloses the production of the diterpenoid alkaloid precursor ent-atiserene in Nicotiana benthamiana co-expressing SEQ ID NO:3 with the Type I terpene synthase DgrTPS1 (Fig. 3A; p. 54, lns. 6-17) and the production of aldehydes and the depletion of ent-atiserene in N. benthamiana co-expressing SEQ ID NO:3 with DgrTPS1 and SEQ ID NO:9 (p. 56, lns. 19-31; p. 57, lns. 1-13). The specification also discloses that different cytochrome P450s produce distinct reaction products when expressed with SEQ ID NO:3 and DgrTPS1 without another cytochrome P450 enzyme (p. 56, lns. 19-31) in comparison to when co-expressed with SEQ ID NO:3, DgrTPS1, and another cytochrome P450 enzyme (p. 57, lns. 1-13). However, Applicant does not disclose the production of diterpenoid alkaloids or diterpenoid alkaloid precursors by an expression system encoding only SEQ ID NO:3 and SEQ ID NO:9, in the absence of a Type I terpene synthase, as encompassed by the claims. The specification also does not describe the in vivo production of diterpenoid alkaloids in an expression system not comprising a N. benthamiana host cell nor the in vitro production of diterpenoid alkaloids.
Regarding claim 1, the recited expression system is not supported by a specific asserted utility. The specification discloses the production of diterpenoid alkaloids only in an expression system comprised within a N. benthamiana host cell. No function is disclosed for an expression system encoding only SEQ ID NO:3 and SEQ ID NO:9. The specification does not disclose any diterpenoid alkaloids produced by an expression system encoding only SEQ ID NO:3 and SEQ ID NO:9. Furthermore, the specification indicates a requirement for at least two distinct classes of terpene synthase in the biosynthesis of diterpenoid alkaloids (p. 06, “Scheme 1”). Thus, it is unknown if an expression system encoding only one terpene synthase produces any diterpenoid alkaloids at all. Likewise, it is unpredictable if unknown compounds will have any utility. In the absence of this information, the real-world use of an expression system having one expression cassette encoding one terpene synthase having at least 95% sequence identity to SEQ ID NO:3 and one cytochrome P450 enzyme with at least 95% sequence identity to SEQ ID NO:9 is unknown and unpredictable. The claimed expression system is not supported by a substantial utility because the specification does not state the function of diterpenoid alkaloids produced by an expression system encoding only SEQ ID NO:3 and SEQ ID NO:9, nor does the specification state if an expression system lacking a Type I terpene synthase produces any diterpenoid alkaloids at all. It is apparent that further basic research is required to make this determination.
The U.S. Supreme Court in Brenner v. Manson, Supreme Court of the U.S. 148 USPQ 689 (1966) made it clear that to meet the utility requirement under 35 U.S.C. 101, an invention must be useful in its currently available form, by indicating, “This is not to say that we mean to disparage the importance of contributions to the fund of scientific information [383 U.S. 519, 536] short of the invention of something “useful,” or that we are blind to the prospect that what now seems without “use” may tomorrow command the grateful attention of the public. But a patent is not a hunting license. It’s not a reward for the search, but compensation for its successful conclusion.” The instant application provides only a starting point for the hunt. It does not reach a conclusion. Because the claimed invention is not supported by a specific and substantial asserted utility for the reasons set forth above, credibility has not been assessed. While the specification indicates that SEQ ID NO:3 comprises a functional Type II terpene synthase and SEQ ID NO:9 comprises a functional cytochrome P450 enzyme, no information is provided regarding the function of an expression system encoding only SEQ ID NO:3 and SEQ ID NO:9. Neither the specification as filed nor any art of record discloses or suggests any property or activity for the products of an expression system encoding only SEQ ID NO:3 and SEQ ID NO:9 in the absence of a Type I terpene synthase.
Claim 2 further limits claim 1 in requiring the expression system comprise at least two expression cassettes. However, this limitation does not address the deficiency regarding the lack of a specific and substantial asserted utility or a well-established utility because an expression system comprising at least two expression cassettes encompasses expression systems consisting of only two expression cassettes. As discussed above, no information is provided regarding the function of an expression system encoding only one terpene synthase (SEQ ID NO:3) and SEQ ID NO:9. Thus, claim 2 is also rejected for lacking a specific and substantial asserted utility or a well-established utility.
Regarding claim 3, the recitation of an additional expression cassette encoding an enzyme for the synthesis of GGPP does not address the deficiency regarding the non-functionality of an expression system encoding only one terpene synthase (SEQ ID NO:3) and SEQ ID NO:9. Thus, claim 3 is also rejected for lacking a specific and substantial asserted utility or a well-established utility.
Regarding claims 4-6, the recitation of a constitutive, inducible, or tissue-specific promoter does not address the deficiency regarding the non-functionality of an expression system encoding only one terpene synthase (SEQ ID NO:3) and SEQ ID NO:9. Thus, claims 4-6 are also rejected for lacking a specific and substantial asserted utility or a well-established utility.
Regarding claims 7-11, the recitation of a host cell, including plant cells, and host cells further comprising an additional expression cassette encoding an enzyme for the synthesis of GGPP do not address the deficiency regarding the non-functionality of an expression system encoding only one terpene synthase (SEQ ID NO:3) and SEQ ID NO:9. It is unknown if the host cells comprise an appropriately functional Type I terpene synthase. Thus, claims 7-11 are also rejected for lacking a specific and substantial asserted utility or a well-established utility.
Response to Arguments – Claim Rejections - 35 USC § 112(a)
9. Applicant’s arguments and amendments filed August 25, 2025 have overcome the written description rejections of record. However, said amendments are insufficient to overcome the rejections of record due to a lack of enablement resulting from the lack of utility as described above.
Because the claims still lack utility, Applicant’s arguments and amendments are not persuasive and are insufficient to overcome the lack of enablement rejection of record. Accordingly, this rejection is maintained.
Claim Rejections - 35 USC § 112(a)
Enablement
10. Claims 1-11 are also rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. Specifically, because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
The U.S. Court of Appeals for the Federal Circuit also agreed that the enablement requirement is not met when the claimed invention does not have a specific and substantial utility. See In re Fischer, 76 USPQ2d 1225 (CA FC 2005).
Conclusion
11. No claim is allowed. The closest prior art, Douchin et al. (US-10982249-B2, published 04/20/2021 (A)), teaches a recombinant host cell comprising: a gene encoding a polypeptide capable of synthesizing GGPP from farnesyl diphosphate and isopentenyl diphosphate; a gene encoding a polypeptide capable of synthesizing ent-CPP from GGPP; a gene encoding an polypeptide capable of synthesizing ent-kaurene from ent-CPP; a gene encoding a polypeptide capable of synthesizing ent-kaurenoic acid from ent-kaurene; a gene encoding a polypeptide capable of reducing cytochrome P450 complex; and/or a gene encoding a polypeptide capable of synthesizing steviol from ent-kaurenoic acid (paragraph 9). Douchin does not teach SEQ ID NO:3 or SEQ ID NO:9.
12. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Examiner’s Contact Information
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEQUANTARIUS JAVON SPEED whose telephone number is (703)756-4779. The examiner can normally be reached M-F; 9AM-5PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad Abraham can be reached on (571)-270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DEQUANTARIUS JAVON SPEED/Junior Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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